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The Effects of Early Postnatal Diuretics Treatment on Kidney Development and Long-Term Kidney Function in Wistar Rats

Ruud R G Bueters1, Annelies Jeronimus-Klaasen, Nuria Maicas

  • 1Department of Pediatric Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.

Nephron
|January 26, 2016
PubMed

Insights

Neonatal diuretics furosemide and hydrochlorothiazide (HCTZ) did not impact kidney development. However, extrauterine growth retardation (EUGR) impaired kidney development in rat pups, but did not alter diuretic effects.

Area of Science:

  • Neonatal physiology
  • Developmental nephrology
  • Pharmacology

Background:

  • Diuretics are commonly used in neonates for fluid management.
  • The impact of clinical diuretic doses on neonatal kidney development and function requires investigation.
  • Extrauterine growth retardation (EUGR) may modulate the effects of diuretics on kidney development.

Purpose of the Study:

  • To determine if clinical doses of furosemide and hydrochlorothiazide (HCTZ) affect kidney development and function in neonatal rats.
  • To investigate whether EUGR influences the effects of these diuretics on kidney development and function.

Main Methods:

  • Wistar rats were cross-fostered into normal or food-restricted litters and treated with saline, furosemide, or HCTZ from postnatal day 2 to 8.
  • Kidney development was assessed by evaluating proliferation, apoptosis, gene expression, glomerular counts, and histopathology.
  • Kidney function was evaluated by measuring clinical pathology parameters, creatinine clearance, plasma creatinine, and blood pressure over 9 months.

Main Results:

  • Furosemide and HCTZ treatments did not significantly alter kidney development or function parameters.
  • EUGR resulted in lower body weight, fewer glomerular generations, and reduced glomerular numbers.
  • EUGR led to higher creatinine clearance and lower plasma creatinine at later time points.

Conclusions:

  • Clinically relevant doses of furosemide and HCTZ do not appear to affect kidney development or function in neonatal rats during active nephrogenesis.
  • EUGR independently impairs kidney development but does not modify the effects of furosemide or HCTZ on the developing kidney.
Abstract

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